Endocrine screening in 32 consecutive patients with hypospadias

Purpose: Various endocrine studies performed in the hypospadias population show an unsatisfactory response to the human chorionic gonadotropin (HCG) test and abnormal androgen biosynthesis with possible enzyme defects. We evaluated the incidence of disorders in androgen production in boys with isolated hypospadias. Materials and Methods: A total of 32 consecutive children (46,XY) with hypospadias were prospectively enrolled in the study. Severity of the defect was assessed with a new classification based on the location of the division of the corpus spongiosum. Endocrine evaluation consisted of measuring luteinizing hormone, follicle-stimulating hormone, anti-mullerian hormone (AMH), testosterone, dihydrotestosterone, progesterone, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, dehydroepiandrosterone sulfate and Delta(4)-androstenedione. In all but 3 patients gonadal stimulation with 1,500 IU HCG every other day for 12 days was performed and steroid concentrations were reassessed after the test. Am adrenocorticotropic hormone test was performed in 2 patients and molecular study of the androgen receptor was performed in 28. Results: An increase to 37.37 nmol./l. progesterone (normal 0.1 to 0.5) and 17alpha-hydroxyprogesterone to 25.48 nmol./l. (normal 1.18 +/- 0.66) before HCG stimulation was noted in 1 patient. These abnormal results were not found after HCG stimulation but reappeared after the adrenocorticotropic hormone test. This result might be related to a partial mix of 17alpha-hydroxylase/17,20-lyase deficiency but no mutation was found after complete sequencing of gene CYP17. Of the 32 patients 4 had an insufficient response to HCG stimulation (testosterone less than 10 nmol./l.), including 1 with a low AMH level of 180 pmol./l. (normal 451 +/- 198) and an increased dehydroepiandrosterone sulfate level of 1,995 nmol./l. (normal 59 +/- 41) before HCG stimulation. Partial androgen insensitivity was suspected in 1 patient because he had a high testosterone response (29.96 nmol./l.) after HCG stimulation but no mutation of the gene of the androgen receptor was detected. Two patients with proximal hypospadias had isolated decreased AMH levels, which was evidence of Sertoli cell insufficiency. Conclusions: Although our series of 32 patients had several abnormal endocrine screenings, these results indicate no significant endocrine defects.